SE453664B - DIBENS (CD, F) INDOLD DERIVATIVES AND A PHARMACEUTICAL COMPOSITION FOR USE AS ANTIPARKINSON OR ANTIDEPRESSIVE AGENT - Google Patents

Description

10 453 664 R 1 is preferably methyl.

When R 2 is an alkyl group, it preferably contains 1 to 4 carbon atoms and is especially n-propyl.

Suitably R preferably has 2 or 3 carbon atoms and is especially ethyl.

A group of precursors according to the invention comprises those compounds with formula I as defined above where R 2 is (C 1_¿¿) all as racemate or optical (4S, 5aR) isomer.

Physiologically hydrolyzable and acceptable esters are esters that can hydrolyzed under physiological conditions to give the corresponding 9,10- dihydroxy-dibenz [cd, f] indole. Such esters include esters of monocarboxylic acid. acids, especially aliphatic or monoaromatic carboxylic acids of the formula R'COOl-l * "i s ré ' where R 'is (C1-17) alkyl, (C3-6) cycloalkyl, phenyl, phenyl which is mono- or independently disubstituted by chlorine, fluorine, trifluoromethyl, (C 1-6 alkyl or (C 1-4) - alkoxy, unsubstituted benzyl or benzyl which is mono- or independently di- substituted with chlorine, fluorine, (C 1-4) alkyl or (C 1-8) alkoxy. (11Rx, 5aSx) -The compounds of the invention of formula I can be prepared read by man ~ - -f »~ e a) preparing a (4Rx, 5aSx) compound of formula I or an acid addition salt thereof by cleavage of the ether groups in a (llRxßaâiÜ compound with the formula ll 2 m) z // RZ \ 'R3 where R 1 to Ra have the above definition, and the Z groups are the same or different and are cleavable ether groups, or a precursor thereof, or b) produces a physiologically hydrolyzable and acceptable ester of a (4Rx, 5aSx) compound of the formula I or an acid addition salt thereof by acylating a corresponding (IIRxßaSÜ compound of formula I, and ' extracts (llRxßaSiñ compound of formula I or a physiological) hydrolyzable and acceptable ester as such or as an acid addition salt of the compound or ester. l0 453 664 3 The cleavage process can be performed in a conventional manner for cleavage. ether groups. For example, the reaction may be carried out by treatment with a strong mineral acid, e.g. aqueous hydrobromic or hydroiodic acid. temperatures may be from 100 ° C or higher, preferably from 100 ° C to the boiling point of the reaction mixture, especially at about IBOOC.

Suitable The ether group Z is preferably (C 1-4) alkyl.

A compound of the invention may be converted into another compound according to the invention in a conventional manner. For example, the hydroxy groups in The 9.1 O positions are acylated.

The acylation can be performed in a conventional manner for selective acylation of phenolic groups in the presence of an amine function. For example, one can as acylating agents use a functional derivative of an acid such as an acid chloride, acid bromide or an acid anhydride. Conveniently, the reaction is carried out by causes an acid chloride to react in the presence of trifluoroacetic acid at temperatures from ° C to the boiling point of the reaction mixture or in the presence of pyridine at tours from 0 ° C to room temperature. (4Rx, 5aSx) -The compound of formula II above and acid addition salts thereof can be prepared by reducing compounds of formula III (111) where Z, RI, Rz and RB have the above definition, or a precursor thereto, and recovering the desired (IIrxJaSU compound of formula II as such or as an acid addition salt thereof.

The reduction can be carried out in a conventional manner, suitably under acid conditions suitable for acidic reduction of enamines or imines, e.g. with zinc in an aqueous mineral acid, preferably hydrochloric acid, suitably in the presence of a mercury (Ilk salt, eg mercury (II) chloride. The reaction may conveniently be carried out in the presence of, for example, ethanol. Suitable temperatures can range from 50 ° C to the boiling point of the reaction mixture.

As used herein, the term precursor refers to compounds that can converted to the starting materials in a conventional manner, e.g. temporarily protected associations. 453 664 4 The resulting compounds of the invention can be recovered from the reaction mixture and purified in a known manner. The free base forms of the compounds according to the invention, comprising the compounds of formula I and esters thereof and compounds of formula II, and including compounds as specific exemplified below, can be converted to acid addition salt forms at conventional nationally and vice versa. Suitable acids for salt formation include e.g. hydrochloric acid.

Racemic compounds of the invention may be obtained from racemic starting material. Optically active isomers can be obtained from optically active precursors or of the racemate. The enantiomers can be obtained from the racemate with known methods, e.g. by fractional crystallization of diastereoisomers salts, e.g. their salts with (+) - di-0,0-p-toluoyl-D-tartaric acid or. (-) - di-0,0-p- toluoyl-L-tartaric acid. Racemic division into the optically active isomers can performed in the final step or in some earlier step in the synthesis, e.g. before cleavage of the ether groups, e.g. in a compound of formula II.

The starting materials of formula III can be prepared as follows reaction scheme: 455 664 (V) (IV) R NH “cPÜH / ÛOUmidâlOi) 2 Qllgf czÜs9§ ° 2å ° “: Rp Hâ] Ri z Û pmm ÛQ ”m_- (V1) (VII) nu-co-nå l! n-butylithium ' "in toz / Na2so4 ...__- g Z G05 ° m * -n (VIII) 3 _, Rzqgqgr or Rz-Li (111) Rz, Ra and Z the above In the reaction scheme, the groups RI, is bromine. definition, R'3 is hydrogen or methyl or ethyl and Hal is chlorine or The reactions can be carried out in a conventional manner, and the products from them can be isolated and purified in a known manner. the above reactions the Z groups preferably In the above-mentioned meian products, e methoxy. 453 664 6 to the extent that the production of any special starting material does not exist specifically described, this can be performed on. conventional way or analogously methods described below for analogous compounds. In the following Examples, all temperatures are given in degrees Celsius and uncorrected.

Example 1: 11,5,5a, 6-tetrahro-910-dihroxy- 1- (i) (uR *, sas “) - s-e: 1- fl) â-suiaeääáii fl sfeu-é-_ffftwl-åe fl = æsss fl_ A mixture of 400 ml (2.87 M) of trifluoroacetic anhydride and # 00 ml (5.22 M) trifluoroacetic acid is added at room temperature under a nitrogen atmosphere 61.1 g (0.206 M) of 3,4-dimethoxy-6-methyl-phenanthrene-5-carboxylic acid, and the mixture stir for 10 minutes. After the mixture has cooled to -5 °, it is added carefully 16.08 g (0.2 # 7 M) of sodium azide in solid form. the mixture is stirred for 2 hours at 0 °, pour on ice, extract three times with methylene chloride and wash with 1N solution of sodium hydroxide. The aqueous phases are extracted twice with methylene chloride / 2-propanol 8: 2. The organic phases are combined, dried and evaporated, giving white crystals. 86 g of the resulting mixed anhydride are heated Hours under reflux in 800 ml of a 2N solution of sodium hydroxide and 800 ml of ethanol, and the mixture is evaporated. The residue is washed with water / ice and extracted three times with methylene chloride. The organic phases are combined, dried and evaporated to give the title compound as an oil. b) â-seeryl fl ml fl s-êi.a fl iffstaëkßfnauésnafßæa (compound of formula V1) 105.7 ml (0.750 M) of N-ethyl-N, N-diisopropylamine are added to a solution of 100, Zg (0.375 M) 9-amino-3β-dimethoxy-G-methyl-phenanthrene in 1000 ml of methylene- chloride. To the resulting mixture is added dropwise over 30 minutes one solution of 34.5 ml (0.1 + 5 M) of acetyl chloride in 250 ml of methylene chloride. During the addition the temperature of the reaction mixture is kept at 20 ° by cooling with ice. Reactional the mixture is stirred for 2 hours at room temperature and extracted with methylene chloride. The organic phases are washed with ice-cold 2N hydrochloric acid, water and 2N sodium bicarbonate, dried over sodium sulphate and evaporated to give the title association. M.p. 190-192 ° after crystallization from acetone / ether. c) octylgylamino-3,4-dimethoxy-G-methyl-phenanthrene (compound of formula V11) 1700 ml (2.05 M) 2096 solution of diisobutylaluminum hydride in toluene at room temperature for a period of 45 minutes to a suspension of 105.7 g (0.3l & 2 M) 9-acetylamino-3, anhydrous tetrahydrofuran. The mixture 7 1-dimethoxy-6-methyl-phenanthrene i 453 664 1500 ml then heated while stirring during nitrogen atmosphere for 2 hours at 80 °. Then the reaction mixture is cooled to 0 ° and under a nitrogen atmosphere, is added portionwise at such a rate that the acidic solution is made alkaline to p1-10 and a mixture of 2500 ml of 2N hydrochloric acid / ice, cooled at -10 °, gas evolution is maintained. The “On addition at o ° of a mer: N sodium hydroxide, and the mixture is extracted three times with methylene chloride / Z propanol 7: 3. The organic phases are combined, washed, which gives the title compound. M.p. 100-120 ° after crystallization from acetone / ether. d) at 0 °, below a dried and evaporated, g-ggyggggiiygipgg o-dimemxy-z-methyl-a-oxo-dabenzjgg 11_f¿d_ ° 1_ (compound of formula IX) 661.4) ml (1.08 μM) of a 1956 μg solution of n-butyllithium in hexane is added 97 g (0.328 M) of 9-ethylamino-3,11-dimethoxy-G-methyl-phenanthrene tetrahydrofuran; the reaction mixture turns dark red. at 0 ° the mixture is transferred in portions -50 ° on a mixture of 500g sodium sulfate and 500g tetrahydrofuran. the mixture on water / ice and extracted three times with ether. e) set for a period of 9 period of 20 minutes and under a nitrogen atmosphere, to a solution of in 1000 ml of anhydrous After stirring for 30 minutes with a Teflon tube with nitrogen pressure at g dry ice in 1500 ml After the temperature of the mixture has reached room temperature, pour methylene chloride. The the combined organic phases are dried over sodium sulphate and evaporated, gives the title association. M.p. l58-160 ° (Sun.) after crystallization from ether / petroleum å-stykl fi fráilysæ-liehzdfexi fl »1 O-dimewXH-mefxtlefrefewk dibelií fl gdzfjindol (compound of formula lll) A solution of 377 ml (4.1 M) of n-propyl bromide in 11 liters of tetrahydrofuran 0 minutes at reflux to 99.8 g (4.1 M) of magnesium span, and the mixture is stirred for one hour at reflux. To the resulting the mixture is added dropwise over 30 minutes and under a nitrogen atmosphere solution of 880 g (2.73 M) of 5-ethyl-Ig5-dihydro-9 (eat lindoi 1 s liter ietrahydfofuran. Reak fi ons , 10-dimethoxy-Z-methyl-11-oxo-dibenzene- the mixture is heated at reflux in 2 hours and then extracted with methylene chloride. The organic phase is washed with a saturated solution of potassium bicarbonate and with water, wipe over sodium sulfate and evaporated to give the title compound (IR spectrum (CH 2 Cl 2): 3540 cm -1 (OH)) step. in) one in the form of a maroon oil .The raw product is used directly for the next Gbea fi ffëfrz-swesazaißefefianidioeaw-d1mewx1-2-max1; ï-Li-_pr_'9py_l-_dil_Jep_s_Lcc_l, f __) in§0_l (compound of formula II) A suspension of 100 g (0.273 M) of S-ethyl-1β-dihydro- ll-hydroxy-'LIO-dime- _____.__ í <- «. ... ......_ _...- __ "" "" "-" '.. "F.V ..' lr l0 453 664 8 Toxi-2-methyl-lean-n-propyl-dibenz [cd, f] indole in 2000 ml of ethanol is added with stirring. to a suspension of 322g ((5928 M) of zinc dust and 71 + +, 3g (0.273 M) mercury OÛ chloride in 2000 ml of distilled water. The reaction mixture is recycled boiled, 450 ml of 1896 g of hydrochloric acid are added dropwise over 15 minutes and the mixture is refluxed overnight with stirring. The mixture is then cooled. to room temperature, filtered and the zinc amalgam washed with 500 ml methylene chloride. The filtrate is made alkaline with 1 liter of concentrated Nl-laOl-1 and extracted three times with methylene chloride (700 ml each time). The merged the organic phases are washed with water, dried and evaporated. The resulting the oil is chromatographed on silica gel using methylene chloride 296 methanol to give the title compound as an oil. o ëuse fi ßasfrzsulssaææ§ = rasidr °; auedihxesxiz-meyi- ï-nææizvl-êiëëiàßßëiåll fl ë fl! ioo g (ï) - (aR *, 5as *) - s- = ty1-4, s, sa, e-fetfanydf ° -9,1o-dameioxa-z-methyl-u- n-propyl-dibenz [cd, f] indole in 1 liter of a 4796-g aqueous solution of hydrobromic acid heated for 6 hours at reflux at a bath temperature of 150 °. After evaporation of the mixture to dryness, the crystalline residue is stirred in acetone and filtered. The precipitate is washed with acetone, then with ether and dried below high vacuum to give the hydrobromide of the title compound. M.p. 200 ° with decomposition. The hydrochloride melts at 185 DEG C. during decomposition.

Example 2: (-) - (4S, 5aR) -5-ethyl-1 +, 5,5a, 6-tetrahydro-9,10-dihydroxy-Z-methyl-β-n-propyl dibens [car hnam (a) L-lsíëàíaßïzå-sšïli fi åifë »é-IQÉEYSßåil fi- šëisëzizë fl lsšll fifl i; afeizyl-fliäs fl slsds fl il fl äl ma g (zu mM) (ïi- (uaïsas fi- s-ethyl-upßas-: etfahydfo-s, io-dxmefoxy- Z-methyl-li-n-propyl-dibenz [cd, f] indole is dissolved in 600 ml of acetone, and a solution of 81.67 g (2 μl mM) (-) - di-0,0'-p-toluoyl-L-tartaric acid monohydrate in 300 ml acetone is added while stirring. The mixture is stirred for another hour at room temperature, with a total of one liter of ether being added portionwise below this period. The resulting precipitate is filtered off, washed with ethyl acetate until remains light yellow and dries. lll +, 7 g of the crystals obtained from the first crystallization is dissolved in 1 liter of Cl-1zCl 2 / methanol 7: 3 at reflux, and the solution is filtered and concentrated until a major portion of the product crystallizes out. The mixture is stirred in about 15 minutes, after which the product is filtered off, washed with ethyl acetate until remains colorless and dried. in 48 g of the product obtained are recrystallized in the same manner with 453 664 9 use of 700 ml of Cl-1zCl 2 / methanol 50:50 to give colorless crystals.

The obtained crystals are recrystallized in the same manner using of 1.2 liters aoolon ooh eu ml methanol. One thus obtains l-Hllsßalu-s-alyl- 4,5,5a, 6-tetrahydro-9,10-dimethoxy-Z-methyl-11-n-propyl-dibenz (cd, f] indole - (-) - di- Oβ-p-toluoyl-L-tartrate in the form of colorless crystals melting at 185-198 °; (o = 0.51 -50 ° (o = 0.51 methanol). b) i-klilâlâaßl; í-sfxlail fi l fi slé-.tëëävslisåalíl-slälxdvzkärasfxlfl; n-lzæeli-éiëf fl-: Lsafjäláfl By proceeding as described in Example lg), one obtains (-) - (4S, 5aR) -5-ethyl-11,5,5a, 6-tetrahydro-9,10-dihydroxy-Z-methyl-1β-n-propyl-dibenzene (cd, phenol-hydrobromide of the tartrate obtained under a) above. Corresponding hydrochloride melts at over 160 ° during decomposition; [t fl so = -9l + ° (c = 0.5 i methanol).

Example 3: (_43 Éåašïl-Bálšêléïeífêln / ÉFS-ållQ-Éïhl / Eßëizëf flfl l fl zí * lídšrfrlâfßlzykëlle fl ä icflšlïndßL (fxalz *, sas *> - ßnsßans-falfanyofo-zlo-olmafoxy-z-molyl-lns-ol-n-propyl- dibenz [cd, f] indole, (oil), is obtained analogously to the method of Examples 1a to f).

This compound is converted to the (-) - (# S, 5aR) -isomer form. Sintering of hydrochloric it at 2100 and melting at 222-222l + °; [α] 25 D = -1270 (c = 0.5 in methanol).

In a manner analogous to Example 2, there is obtained (-) - (11S, 5aR) -1 #, 5,5a, 6-tetrahydro- 9,10-dihydroxy-Z-methyl-11H-di-n-propyl-dibenz (cd, phenol hydrochloride. Mp above 145 ° with decomposition; u u = = -82.2 ° (c = 0.45 in methanol).

It should also be noted that 9-amino-3,11-dimethoxy-β-methylphenanthrene can is converted directly to 9-ethylamino-3β-dimethyloxy-6-methyl-phenanthrene by heating with ethylamine in Z-ethoxyethanol.

The compounds of the invention, in particular the compounds of formulas I and li, and their pharmaceutically acceptable acid addition salts are pharmacological activity in animals and are therefore indicated for use as medicinal products. Particularly the compounds are indicated for use as central dopaminergic stimulants means, as shown by standard experiments, e.g. according to the method according to U. Ungerstedt a: al [Acta Physlol. soano. suppl. (1971), 337, soppl. 66-93), by induction of contralateral rotation of appreciable duration in rats (whose substantia nigra damaged by a microinjection of δ-hydroxy-dopamine for one week earlier) after i.p. and p.o. administration in an amount of 0.03 to about 10 mg / kg animal body weight. The activity is confirmed by developing stereotyped sniffing, licking and biting behavior in rats according to following test after i.p. administration in an amount of 1 to 30 mg / kg of animal body weight. dose dependent 4 5 5 6 6 4 Rats, 180-222 g, are placed in plexiglass cylinders with a diameter of 30 cm a wire mesh floor. After 30 minutes to allow acclimatization to the cage inject the rats with the compound to be tested. Râttornas behavior is observed for 2 minutes at 30 minute intervals for 2 hours and then at 60 minute intervals for a total of up to 7 hours. The grade of observed stereotyped behavior is determined using a valuation system based on that described by Costall, Nayler and Olley (Europ. J.

Pharma. _1_s_, 83-94, (1972)]. the valuation and criteria are as follows: l. Intermittent sniffing 2. persistent sniffing, temporary licking 3. Licking, temporary biting Intense and persistent biting.

The central dopaminergic activity is also strengthened by inhibition of catalepsy induced by reserpine in mice upon subcutaneous administration of approx 0.01 mg to about 2 mg / kg of the compounds.

It will be appreciated that the compounds of the invention are carboxylic acyloxy substituents can be hydrolyzed under physiological conditions to give corresponding active hydroxy compounds according to the invention.

For the compounds of the invention, in particular the compound of Examples 2, in addition, this central dopaminergic activity is specific as shown at in in vitro tests by non-affinity for clonidine receptors with using the method described by A. Closse et al in “Psychopharmac- cology and Biochemistry of Neurotransmitter Receptors ", HJ. Yamanura, R.V.

Olsen and E. Usdin, Edition, Elsevier North Holland Inc., Amsterdam, 1980, p. 063-065. This specificity is confirmed by a weak prolactin secretion inhibitor. activity and insignificant emesis in dogs at appropriate doses for central dopaminergic activity.

The compounds are therefore indicated for use as central dopamines. nerga means, e.g. for the treatment of Parkinson's disease. An indicated daily dose is from about 4 to about 30 mg, suitably administered in divided doses 2 to 4 times per day in unit dosage form containing from about 1 to about 15 mg of the compound, or in extended release form.

The compounds of the invention, in particular the compounds of formula I, are further indicated for use as antidepressants, as shown by inhibition of catalepsy induced by reserpine in mice during subcutaneous administration by administering about 0.01 mg to about 2 mg / kg of the compounds and by inhibiting the catalepsy induced by tetrabenazine in rats during oral administration . 453 664 ll of about 5 to about 20 mg / kg of the compounds.

An indicated dose for this indication is from 0.05 to about 2 mg, preferably administered in sub-doses 2 to 4 times a day in unit dosage form containing from about 1 to about 15 mg of the compound, or in extended form release.

The preferred indication is the antiparkinsonian indication. The the drawn compound is the compound of Example 2.

Compared to known compounds with antiparkinsonian activity, according to the invention a much more advantageous action profile with a powerful antidepressant component, selective dopaminergic activity with negligible effect on the adrenergic system and better tolerance.

This was shown e.g. in comparative experiments between, on the one hand, the compounds of Examples 2, i and 3 above (hereinafter referred to as compounds A, B) resp. C) and the compounds according to Examples 4, 3 and 5 in the Swedish patent specification 8103983-6 (hereinafter referred to as compounds a, b and c, respectively).

Thus, compound A at 5 mg / kg p.o. about the same size central dopaminergic stimulating activity when measured in rats according to U. Ungerstedt et al as compound a at 3 mg / kg p.o. At 1.0 mg / kg i.p. developed compound B significant activity, which was slightly less than for compound b.

In stereotype tests on rats as described previously developed compounds A, B and C less stereotyped than compounds a, b and c and is therefore expected to cause minor side effects, such as dyskinesia, in humans.

Furthermore, in determining antidepressant activity by measurement of the ability of the compounds to inhibit reserpine-induced akinesia (essential as described by J. M. Vigouret et al., Pharmacology 26 (Suppl. 1), 156- 173 (1978)) compound A significantly longer action than compound a and had after 5 hours 6 times the activity of compound a (ED 50 0.375 mg / kg s.c. for A against 2.3 mg / kg s.c. for a).

In in vitro clonidine binding assays in rats according to V. Prichard, D. C. et al, Moi. Pharmacol. _12, 454/1977, the association showed a strong affinity for the binding sites for clonidine (IC 50 = 31 nmol), while the compounds A, B and C had weak affinity (IC 50 = 2050, 1700 and 665 nmol, respectively) and therefore is more selective for the dopamine binding sites.

Tests performed on the cardiovascular system on pentotal anesthesia cats showed that compound A in contrast to compound a practically did not showed some effect on blood pressure and less pronounced tendency to decrease heart rate. In addition, compound A gave less change in reaction to noradrenaline and carotid artery occlusion other than compound a. In response to isoprotein 453 664 12 renol had no significant effect in compound C at a cumulative dose of 37.44 gig / kg (+ l196), while compound a potentiated it by isoproterenol significantly decreased blood pressure 96696). These results were confirmed by the effects on corneal tone, where compound A in a cumulative dose of 37.114 ug / kg increased tone with 23996 compared to 9896 for compound a. Compound A therefore has better tolerance than compound a.

The better tolerability of compound A compared to compound a was confirmed by less prolactin secretion inhibition and less emesis. Thus showed compound A in determining the ability of the compounds to inhibit implantation. rat as described in Experentia _32, 1330-1332 (1978), a 5050 of 0.87 mg / kg s.c., while compound a had 0.034 mg / kg s.c. ED yes value for emetic effect, i.e. the dose which, by conventional determination, causes vomiting in 5096 of the animals, was 11 μg / kg i.v. for compound A and 2.9 ug / kg for compound a.

The compounds may be administered in the form of pharmaceutically acceptable acid addition salts. These salt forms show the same kind of activity as it free base form.

The present invention also relates to a pharmaceutical composition which contains a compound of formula I according to the invention, a physiological one hydrolyzable and acceptable ester thereof, or a pharmaceutically acceptable acid addition salt thereof, in combination with a pharmaceutically acceptable diluent agent or a pharmaceutically acceptable carrier.

These compositions may be formulated in conventional manner to form for example a solution, a capsule or a tablet.

Claims (9)

10 15 20 25 453 664 13 PATENT REQUIREMENTS l. (Ii fi SaSU-fluorine of formula III 3 R OH II l <<1) H0 \ / q / Rz, 'RB where R1 is (C (C 3-7) cycloalkyl- (C 1-4) alkyl, and Ra is (C 1-5) alkyl, or a physiologically hydrolyzable and acceptable ester thereof, or an acid addition salt of the compound or ester. A compound according to claim 1, wherein R 2 is (C 1-3) alkyl and R B is (C 1-3) alkyl, as racemate or as optical (4S, 5aR) isomer, or an acid addition salt of racemate or isomer. A compound according to claim 1, characterized in that it is an fi-s-ethyl-: nspas-: exranydfa-s, io-dihydroxy-2-methyl-11-n-propyldibenz [cd, í] indole or an acid addition salt hence. A compound according to claim 1, in that it is WR 1, Sa 2 SO 4 -β, 5,5a, 6-tetrahydro-2-methyl-9,10-dihydroxy-11H-di-n-propyldibenz (cd, 1] indole or an acid addition salt thereof A compound according to claim 1, in that it is (45.5aR) -5-ethyl-11,5,5a, 6-tetrahydro-9,10-dihydroxy-Z-methyl-β-n-propyldibenz [cd, f ] indole or an acid addition salt thereof. characterized A compound according to claim 1, in that it is (45.5aR) -1 +, 5.5a, 6-tetrahydro-9,10-dihydroxy-2-methyl-11H-dl-n-propyldibenz [cd, f] indole or an acid addition salt characterizes! hence. A compound according to any one of claims 1 to 6, or a pharmaceutically acceptable acid addition salt of the compound for use as a medicament. A compound according to any one of claims 1 to 6, or a pharmaceutically acceptable acid addition salt of the compound for use as an antiparkinsonian or antidepressant. Pharmaceutical composition, characterized in that it comprises a compound of formula I 1 OH I \ (I) HDX / 4 / R 2 -RB fa where R 1 is (Chulalkyl, R 2 is hydrogen, (C 1-7) alkyl, (C 3-7) cycloalkyl or (C 3-7) cycloalkyl- (C 1-4) -alkyl, and R B is (C 1-5) alkyl, or a physiologically hydrolysable and acceptable ester thereof, or a pharmaceutically acceptable acid addition salt of the compound or ester, in association with a pharmaceutical carrier or a pharmaceutical diluent.